Article

Placental mosaicism and survival of trisomies 13 and 18

Department of Pathology and Medical Genetics, University of British Columbia, Vancouver, Canada.
The American Journal of Human Genetics (Impact Factor: 10.99). 04/1989; 44(3):338-43.
Source: PubMed

ABSTRACT Cytogenetic analysis of 14 placentas from live newborn infants or from terminated pregnancies with trisomies 13 and 18 revealed that all were mosaic. The mosaicism was confined to the cytotrophoblast and not detected in villous stroma, chorionic plate, or amnion. The percentage of cells with a normal karyotype varied from 12% to 100%, the average being 70%. No such confined mosaicism could be detected in 12 placentas of trisomy 21 fetuses. These findings suggest that a postzygotic loss of a trisomic chromosome in a progenitor cell of trophectoderm facilitates the intrauterine survival of trisomy-13 and -18 conceptuses. They also imply that it is placental function which determines the intrauterine survival and that the mother plays no active role in rejection of trisomic conceptions. The combination of both a pre- and post-zygotic cell division defect in viable trisomy-13 and -18 conceptions points to the possibility of a genetic predisposition to such events. The detection of only a diploid cell line in the cytotrophoblast of some pregnancies with trisomies 13 and 18 also suggests that direct preparation is unreliable for prenatal diagnosis of these trisomies on chorionic villi sampling and that long-term villous culture should be used.

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    • "Irrespective of their incidence, all autosomal trisomies seem lethal to embryonic or fetal development with only a few exceptions. For example, approximately 75–80% of trisomy 21, more than 95% of trisomy 13 or 18, and 100% of trisomy 16 conceptuses do not survive to term [Kalousek et al., 1989]. Liveborn children with non-mosaic trisomy 22 are extremely rare, and their life span ranged from minutes to 3 years of age with an average survival of four days [Heinrich et al., 2013]. "
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    ABSTRACT: Trisomy 22 is the third most common autosomal trisomy occurring in about 0.4% of all clinically recognized pregnancies. Complete non-mosaic trisomy 22 is extremely rare in live births. Most affected children die before one year of age. To date, only 29 liveborn cases have been reported and none has carried an additional genetic lesion. In this report, we describe the clinical presentation, cytogenetic, and cytogenomic findings in a liveborn female with complete non-mosaic trisomy 22 as well as a paternally inherited, balanced reciprocal chromosomal rearrangement t(4;6)(q33;q23.3). The proband manifested features commonly seen in individuals with non-mosaic trisomy 22 such as intrauterine growth retardation (IUGR), single umbilical artery, cranial abnormalities, short neck, cleft lip and palate, dysmorphic ears, hypoplastic nipples, digital malformation, congenital heart defects, dysplastic kidneys, and genital anomalies. In addition, she had lobar holoprosencephaly, aqueductal stenosis, and limb and eye problems that have not been associated with complete trisomy 22 in previous reports. She died at 35 days of age of complex heart disease and renal failure. We are hereby expanding the cytogenetic and clinical spectrum of this rare chromosome disorder. Clinical features of liveborn children with non-mosaic trisomy 22 are reviewed and compared to those in our proband. The impact of genomic content in relation to the survival of trisomies in humans is also discussed. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 12/2014; 164(12). DOI:10.1002/ajmg.a.36778 · 2.05 Impact Factor
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    • "In all three types, the mosaicism is confined to the placenta and the fetus is normal [7]. Fetal growth retardation and death were shown to be associated with an increasing proportion of aneuploidic cells in the placenta and placental lineage, even when the chromosomal anomaly is exclusively confined to the placenta, suggesting a major influence for the placenta on abnormal fetal development [9–11]. Abnormal placentation early in pregnancy results in restricted blood flow to the placental-fetal unit. "
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    ABSTRACT: We present a case of fetoplacental discrepancy in a second-trimester fetus with normal karyotype in amniotic fluid and two different Robertsonian translocations in placenta. A 41-year-old woman of Middle-Eastern origin, gravida 2, para 1, underwent amniocentesis at 16-week gestation because of advanced maternal age. Amniotic fluid karyotype showed a normal 46,XX karyotype with a homozygous inv(9). Parental chromosome analysis showed both parents to be carriers of inv(9) and the parents are not consanguineous. Fetal ultrasound was normal. The mother presented to the clinic 4 weeks later with intrauterine fetal demise. Chromosome analysis from the placenta showed two different cell lines: a balanced (15;21) Roberstonian translocation in 11 cells and an unbalanced (21;21) Robertsonian translocation in 9 cells. The karyotype was interpreted as mos 45,XX,inv(9)(p11q13)x2,der(15;21)(q10;q10)[11]/46,XX,inv(9)(p11q13)x2,+21,der(21;21)(q10;q10). Mother was a carrier for the Cystic Fibrosis (delta F508), Factor V Leiden mutations, HbD-Los Angeles and HbQ-India variants. She also had a sibling with term stillbirth. Her husband's history was unremarkable. Our case appears to be another example of confined placental mosaicism (CPM) with normal fetal karyotype. However, we could not confirm the possibility that CPM contributed to the IUFD in our case given the complex medical history of the mother.
    06/2013; 2013:951710. DOI:10.1155/2013/951710
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    • "In twin B described herein, where the presence of a trisomy 18 was suspected by MRA analysis, and confirmed cytogenetically both in CVS-LTC and postpartum placenta (low mosaic), a type III CPM is supposed to be present. Type III CPM has been reported to provide biological protection for trisomy 18 conceptuses and facilitate their intrauterine survival [Kalousek et al., 1989]. This is reinforced by the fact that USE anomalies found in the first trimester resolved spontaneously with no other abnormalities found in subsequent USE and is an indication of a favorable outcome. "
    American Journal of Medical Genetics Part A 06/2013; 161A(6). DOI:10.1002/ajmg.a.35902 · 2.05 Impact Factor
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